Congenial anomalies of the kidney and urinary tract are common in childhood and may lead to renal failure, infection, and hypertension. In addition, premature infants experience deficits in renal function because of incomplete renal maturation. For these reasons it is important to understand the mechanisms of normal renal development and of congenial anomalies. Mouse models of human disease serve as useful tools to examine these mechanisms. The applicant has begun to study a model that has early ureteric bud branching defects and an unexpected defect in dorsoventral renal axis formation. Late in development the mice have non-obstructive renal pelvic dilation. This proposal will use the mouse model and organ explant cultures to extend our understanding of the mechanisms leading to renal anomalies and the mechanisms that control normal development. The aims will be to 1) characterize the mechanism leading to pelvic dilation in the mutant; 2) determine the mechanism that controls differentiation of the collecting duct cell subtypes; 3) characterize the mechanism of proximo distal nephron axis formation; 4) to evaluate the potential for environmental regulation of hoax-11 and hold-11 that would produce of a more serve renal anomaly. The applicant for the award is a pediatric nephrologist who has had an interest and previous experience in renal development and who plans a long-term career in studying in the mechanisms of renal organogenesis. The award will allow him to broaden the scope of his research. The applicant has had a productive maundered relationship with a well- established investigator and will obtain help from two other investigators in the institution. The institution has a particularly strong track record in developmental biology and continues to support new research activity in this field. The environment will allow the candidate to achieve his career goals.